PARTICIPATION OF GLOMERULAR ENDOTHELIAL-CELLS IN THE CAPILLARY REPAIROF GLOMERULONEPHRITIS

In many glomerular diseases severe injury to the mesangium may occur, leading to matrix dissolution and damage to the glomerular capillaries . Although the destruction of glomerular architecture may lead to perm anent injury, in some cases spontaneous recovery occurs. The mechanism s that mediate this recovery are unknown. In this study we provide evi dence for glomerular capillary repair (angiogenesis) in the adult inju red glomerulus. Injection of anti-Thy 1 antibody into rats results in severe mesangiolysis with capillary ballooning, microaneurysm formatio n, and loss of endothelial cells in addition to mesangial cells. Altho ugh mesangial proliferation is a major response to injury, proliferati on of endothelial cells also can be documented from days 2 to 14 in as sociation with repair of the capillaries. The endothelial cell prolife ration peaks on days 2 and 7, when it is seven- to ninefold greater th an normal. Many of the endothelial cells display morphological feature s of angiogenesis. The initial wave of endothelial cell proliferation can be reduced by 40% with neutralizing anti-basic fibroblast growth f actor antibodies (P < 0.001). The later glomerular endothelial cell pr oliferation is associated with upregulated expression of vascular perm eability factor/endothelial cell growth factor (VPF/VEGF) and an incre ase of flk, a VPF/VEGF receptor. Although PDGF is expressed in this mo del, anti-PDGF antibody treatment did not affect the endothelial cell proliferative response. In summary, glomerular endothelial cells have an active role in the glomerular response to injury. Glomeruli are cap able of healing microaneurysms, and the mechanism involves basic fibro blast growth factor- and VPF/VEGF-mediated endothelial proliferative r esponses.